Parathyroid Hormone Levels Research Articles

Association Between Vitamin D and Asymptomatic Hyperuricaemia Among Adults––An Observational Study

Introduction: The relationship between Vitamin D levels and asymptomatic hyperuricaemia is gaining attention due to its potential implications for public health. This study investigates this association, focussing on the interplay between Vitamin D, serum uric acid and parathyroid hormone (PTH) levels in adults. Materials and Methods: This cross-sectional observational study, conducted from April to June 2023, involved 100 adult participants (65 males, 35 females) from the general population. Participants were selected based on specific inclusion and exclusion criteria. Data collection included a comprehensive questionnaire, physical examinations and blood sample analysis. Vitamin D levels were measured using liquid chromatography-tandem mass spectrometry, uric acid levels through an enzymatic colorimetric test, and PTH levels via a chemiluminescent immunoassay. Statistical analysis was performed using SPSS version 25.0, IBM Corp, Chicago, IL, USA. Results: The study found an inverse correlation between Vitamin D and serum uric acid levels. Participants with lower Vitamin D levels had higher serum uric acid and PTH levels. The mean serum Vitamin D level was 32.17 ng/mL, and the mean serum uric acid level was 9.99 mg/dL. The study categorised Vitamin D levels as deficient, insufficient and sufficient, observing significant variations in PTH and uric acid levels across these categories. Conclusion: The study suggests a significant relationship between Vitamin D levels and serum uric acid concentrations in adults, with implications for the management of asymptomatic hyperuricaemia and related metabolic conditions. Despite limitations, such as the cross-sectional design and small sample size, this study highlights the potential significance of Vitamin D levels in the management of asymptomatic hyperuricaemia and related metabolic disorders.

Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity

BackgroundChildren with obesity have low 25 hydroxy-vitamin D (25-OH-D3) levels compared to lean children. Recommendations on when to start vitamin D supplementation differ largely between countries. Longitudinal data on 25-OH-D3 levels to guide treatment decisions are scarce since they are largely influenced by solar radiation and are difficult to compare.MethodsWe carried out a retrospective analysis of multiple 25-OH-D3 and parathyroid hormone (PTH) measurements in a cohort of 543 patients without vitamin D supplementation. All measurements were taken at the local paediatric obesity clinic as documented in the German-Austrian-Swiss APV (Prospective Documentation of Overweight Children and Adolescents) registry from 2009 to 2019. Serial 25-OH-D3 and PTH levels were adjusted for sunshine duration over the last 30 days to account for seasonal variation, as well as for sex and body mass index (BMI). We further performed an exploratory analysis of the association of sunshine duration, sex, BMI SDS (standard deviation score), abnormal lipid levels or dysglycemia with the 25-OH-D3 trend.Results229 obese patients (mean BMI SDS: 2,58 (± 0,56), 53% females, mean age: 12 (± 3) years, range: 2–21 years) with two, 115 with three and 96 with four repeated 25-OH-D3 measurements were identified. Mean adjusted 25-OH-D3 (48.2 nmol/l) and PTH (34.9 ng/l) levels remained stable over 120 weeks. 5% of the patients had an elevated PTH > 65 ng/l. High total cholesterol ≥ 200 mg/dl and high triglycerides ≥ 130 mg/dl were associated with higher 25-OH-D3 levels.ConclusionWe propose a simple method to include sunshine duration in the analysis of 25-OH-D3 levels to minimise the bias of seasonal variation. Based on our data we established the pragmatic strategy of limiting vitamin D supplementation to patients with biochemical signs of mineralisation disorders such as elevated PTH and alkaline phosphatase (AP). In children with normal PTH and AP we recommend adjustment of calcium intake and increase of outdoor activity instead.

Pharmaceutical Management of Secondary Hyperparathyroidism and the Role of Surgery: A 5-Year Retrospective Study.

Background and Objectives: Secondary hyperparathyroidism (SHPT) poses a common condition among patients with chronic kidney disease (CKD) due to the chronic stimulation of the parathyroid glands as a result of persistently low calcium levels. As a first option for medical treatment, vitamin D receptor analogs (VDRAs) and calcimimetic agents are generally used. Apart from cinacalcet, which is orally taken, in recent years, another calcimimetic agent, etelcalcetide, is being administered intravenously during dialysis. Materials and Methods: In a 5-year retrospective study between 2018 and 2023, 52 patients undergoing dialysis were studied. The aim of this study is to highlight the possible effects and/or benefits that intravenously administered calcimimetic agents have on CKD patients. A total of 34 patients (65.4%) received cinacalcet and etelcalcetide while parathormone (PTH) and calcium serum levels were monitored on a monthly basis. Results: A total of 29 out of 33 patients (87.9%) that received treatment with etelcalcetide showed a significant decrease in PTH levels, which rose up to 57% compared to the initial values. None of the included patients needed to undergo parathyroidectomy (PTx) due to either extremely high and persistent PTH levels or severe side effects of the medications. It is generally strongly advised that parathyroidectomies should be performed by an expert surgical team. In recent years, a significant decrease in parathyroidectomies has been recorded globally, a fact that is mainly linked to the constantly wider use of new calcimimetic agents. This decrease in parathyroidectomies has resulted in an important decrease in complications occurring in cervical surgeries (e.g., perioperative hemorrhage and nerve damage). Conslusions: Despite the fact that these surgical complications cannot be easily compared to the pharmaceutical side effects, the recorded decrease in parathyroidectomies is considered to be notable, especially in cases of relapse where a difficult reoperation would be considered based on previously published guidelines.

Significant role of 1,25-dihydroxyvitamin D on serum calcium levels after total thyroidectomy: a prospective cohort study.

Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy. Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery. Serum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)2D. The only factor predicting a postoperative 1,25(OH)2D decrease was a high preoperative 1,25(OH)2D concentration. Postoperative 1,25(OH)2D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)2D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)2D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)2D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant. 1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Evaluation of Hypocalcemia Following Total Laryngectomy With and Without Thyroidectomy.

Hypoparathyroidism and associated hypocalcemia are well-established complications following laryngectomy. This study further characterizes the rates of hypocalcemia in patients undergoing total laryngectomy (TL) with and without thyroidectomy and hemithyroidectomy. Retrospective cohort study. TriNetX. We queried TriNetX, a deidentified patient database, to identify patients who underwent TL with and without thyroidectomy and hemithyroidectomy. Rates of hypocalcemia, low parathyroid hormone (PTH), calcium, and calcitriol supplementation were compared between groups with multivariable repeated measures logistic regression. We identified 870 patients in the TL without thyroidectomy cohort, 158 patients in the hemithyroidectomy cohort, and 123 in the total thyroidectomy cohort. Rates of hypocalcemia differed between patients receiving total thyroidectomy versus TL alone for 0 to 1 month (odds ratio [OR]: 2.88 [1.95-4.26]) 1 to 6 months (OR: 5.08 [2.29-11.3]), and 6 to 12 months (OR: 2.63 [1.003-6.88]) postoperatively, with adjustment for age at laryngectomy, race, ethnicity, and gender. Results were similar among those who received calcium supplementation. The rate of low PTH levels differed in these groups for 0 to 1 month (OR: 5.13 [3.10-8.51]), 1 to 6 months (OR: 3.47 [1.46-8.22]), and 6 to 12 months (OR: 3.63 [1.40-9.38]) following surgery. Rates of postoperative calcium supplementation were increased for patients receiving total thyroidectomy versus TL for 1 to 6 months (OR: 2.44 [1.62-3.68]), and 6 to 12 months following surgery (OR: 1.79 [1.18-2.72]). Patients undergoing TL with total thyroidectomy have a higher risk of postoperative hypocalcemia compared to patients receiving TL alone. Risk of parathyroid injury in these patients may warrant further emphasis on PTH measurement after surgery and a multidisciplinary approach to management.

A Mandibular Brown Tumor: A Pediatric Case Report and Summary of Adolescence Cases

Mandibular brown tumors are often radiographically and histologically indistinguishable from cherubism, aneurysmal bone cyst, giant cell granuloma, and odontogenic fibroma. Laboratory findings of hyperparathyroidism (HPT) aid in directing therapy. We present a case of a 14-year-old male with a brown tumor of the mandible associated with secondary HPT due to vitamin D deficiency. Core biopsy exhibited a proliferation of plump spindle cells and osteoclast-like giant cells within variably fibrous stroma. Parathyroid hormone (PTH) levels were elevated to 288 pg/mL (normal 8.5-77.1 pg/mL) and vitamin D was low at a level of 6.9 ng/mL (normal &gt; 20.0 ng/mL). Six months after the introduction of weekly vitamin D supplementation, PTH and vitamin D levels improved but remained abnormal with PTH of 86.8 pg/mL and vitamin D of 9.3 ng/mL. Alongside an improvement in laboratory indices, the tumor character stabilized and became less clinically friable; however, the burden remained unchanged. At 9 months, the patient underwent surgical debulking of the tumor with local soft tissue coverage. A review of pediatric literature was performed, among which 16 patients were identified. Most children who developed brown tumors were found to have secondary HPT and ultimately 44% underwent some degree of surgical debridement of the mass.

Comparison of Serum Vitamin D Level between Outdoor and Indoor Working Professionals and Its Correlation with Serum Parathyroid Hormone Level

Background: Parathyroid hormone (PTH) is functionally linked to vitamin D for calcium homeostasis in our body. Objective: To compare serum vitamin D level between outdoor and indoor working professionals of Dhaka city, Bangladesh, and observe its correlation with serum PTH level. Methods: This cross-sectional, analytical study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka, Bangladesh, from July 2018 to June 2019. A total of 101 indoor and outdoor professional workers of both sexes working in different sectors living in Dhaka city participated in this study. They were divided into two groups –outdoor workers (n=35) and indoor workers (n=66) Estimations of both serum vitamin D3 and PTH were done using chemiluminescence microparticle immunoassay method. Statistical analysis was done by students unpaired t tests and Pearson correlation coefficient test. Results: Among outdoor workers, mostly hailed from Traffic Police Services (83%) and the rest (17%). were street hawkers. Indoor workers were recruited from the hospital – nurses (32%), doctors (27%), administrative employees (21%), hospital ward assistants (12%) and medical technicians (8%). Sufficient and insufficient levels of serum D3 were observed more in outdoor professional workers than indoor (P&lt;0.05) whereas deficient levels of serum D3 was found more in indoor workers than outdoor workers (P&lt;0.001). Mean serum vitamin D3 level was found significantly (P&lt;0.001).higher in outdoor workers than that of indoor workers (19.35±5.67ng/ml vs. 14.17±4.18ng/ml) but mean serum PTH level was not significantly different (P&gt;0.05)r in outdoor workers than that of indoor workers (42.35±18.27 vs. 37.78±17.54); Moreover, there was no significant correlation between serum vitamin D and parathyroid hormone levels in both outdoor (r= +0.290; p &gt;0.05) and indoor (r= –0.206; p&gt;0.05) groups .Conclusion: Our data concluded that indoor working professionals were more prone to develop vitamin D deficiency although outdoor working professionals may be affected with vitamin D insufficiency. In addition, there may be no relationship between serum vitamin D and parathyroid hormone levels even in D deficient indoor workers. J Bangladesh Soc Physiol 2022;17(2): 78-84

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

A giant parathyroid cyst causing primary hyperparathyroidism in a pregnant woman: Case report and literature review

Introduction Primary hyperparathyroidism (PHPT) during pregnancy is rare, with the commonest cause being parathyroid adenoma. Parathyroid cysts represent 0.5% of parathyroid lesions. The diagnosis of PHPT requires elevated levels of calcium, along with elevated or non-suppressed parathormone levels. Conservative treatment prevails unless hypercalcemia persists. Case A 33-week pregnant woman with preeclampsia and a cervical tumor was diagnosed with PHPT due to a functioning cystic adenoma. She underwent a caesarean section at 36 weeks, delivering a low-birthweight live newborn. Six months post-caesarean section the patient underwent right inferior parathyroidectomy and right hemithyroidectomy, with histopathological findings consistent with a giant cyst parathyroid adenoma. At review three months. after surgery, there are no signs of the persistence of the disease. Conclusion A giant functional parathyroid cyst causing PHPT and being identified in pregnancy is exceedingly rare. It is crucial to have a timely multidisciplinary diagnosis and management to avoid maternal and fetal complications.

Analysis of factors influencing vascular calcification in peritoneal dialysis patients and their impact on long-term prognosis

BackgroundThis study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis.MethodsThis retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results.ResultsA total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan–Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients.ConclusionLonger dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.

Iron Indices Mediate but Not Modify Association of Parathyroid Hormone with Erythropoietin Resistance in Hemodialysis Patients

Introduction: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. Methods: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr), and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the correlations of iron indices, PTH, and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. Results: The average ERI value was 10.3 ± 5.3 IU w−1 kg−1 (g/dL) −1. ERI was correlated to PTH, hepcidin, CHr, and TSAT (all p < 0.05). Hepcidin and PTH were closely correlated with each other (r = 0.28, p = 0.020). Analysis by PTH categories yielded a total association effect of 2.53 (95% CI: 0.27–4.85, p = 0.027) for high PTH subgroup versus the reference low subgroup. No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-third of the total association between PTH and ERI in hemodialysis population (33.6%, p = 0.025). Conclusion: Iron indices and PTH levels were related to ERI values. Hepcidin appeared to be closely correlated to PTH and partly mediate the association between PTH and ERI in hemodialysis population.

Self-assembled nanobody-DNA nanomachine conjugate for parathyroid glands intraoperative imaging and parathyroid hormone detection

During thyroidectomy, inadvertent parathyroid damage commonly occurs owing to the varying location of the parathyroid glands and their similarity to adipose tissue, lymph nodes, and thyroid nodules. Therefore, in this study, we aimed to develop a novel self-assembled nanobody-DNA nanomachine conjugate probe (PTH-Nb-HCR) for precisely identifying the parathyroid glands and monitoring parathyroid hormone (PTH) levels in patient blood. The probe consists of two components: the first component is the nanobody (Nb)-nucleic acid conjugate PTH-Nb-Trigger, acting as a recognition unit for PTH and capable of initiating the hybridization chain reaction (HCR), whereas the second component comprises the HCR hairpin probes HP1-FAM (with a modified FAM signal molecule at the 5′ end) and HP2. The assembly of the PTH-Nb-HCR fluorescent probe takes only 20 min. Using the probe, the serum PTH level was quantitatively detected in the 0.1–1000 pg/mL range, and the parathyroid glands were rapidly distinguished from adipose, lymphoid, and thyroid tissues within 5 min. We also used this probe for imaging parathyroid glands with hyperparathyroidism. Considering the strong correlation between fluorescence intensity and preoperative serum PTH levels in patients, we anticipate the use of this probe to distinguish normal and hyperfunctional tissues during hyperparathyroidism surgery.

Rare genetic disorders that impair parathyroid hormone synthesis, secretion, or bioactivity provide insights into the diagnostic utility of different parathyroid hormone assays.

Parathyroid hormone (PTH) is the major peptide hormone regulator of blood calcium homeostasis. Abnormal PTH levels can be observed in patients with various congenital and acquired disorders, including chronic kidney disease (CKD). This review will focus on rare human diseases caused by PTH mutations that have provided insights into the regulation of PTH synthesis and secretion as well as the diagnostic utility of different PTH assays. Over the past years, numerous diseases affecting calcium and phosphate homeostasis have been defined at the molecular level that are responsible for reduced or increased serum PTH levels. The underlying genetic mutations impair parathyroid gland development, involve the PTH gene itself, or alter function of the calcium-sensing receptor (CaSR) or its downstream signaling partners that contribute to regulation of PTH synthesis or secretion. Mutations in the pre sequence of the mature PTH peptide can, for instance, impair hormone synthesis or intracellular processing, while amino acid substitutions affecting the secreted PTH(1-84) impair PTH receptor (PTH1R) activation, or cause defective cleavage of the pro-sequence and thus secretion of a pro- PTH with much reduced biological activity. Mutations affecting the secreted hormone can alter detection by different PTH assays, thus requiring detailed knowledge of the utilized diagnostic test. Rare diseases affecting PTH synthesis and secretion have offered helpful insights into parathyroid biology and the diagnostic utility of commonly used PTH assays, which may have implications for the interpretation of PTH measurements in more common disorders such as CKD.

Impact of COVID-19 pandemic on care of maintenance hemodialysis patients: a multicenter study

BackgroundThe COVID-19 pandemic posed a challenge to hemodialysis (HD) patients. While most outpatient and elective medical services stopped during lockdown, HD patients continued to visit their dialysis centers. We aimed to assess how the initial phase of the pandemic affected patient care by comparing dialysis adequacy and other parameters of patient care before and during the first 10 months of the COVID-19 pandemic.MethodsIn a retrospective multi-center observational study, all adult dialysis patients in five dialysis centers in Alexandria, Egypt were included. Dialysis adequacy, missed sessions, laboratory parameters and hospitalization were recorded. Data of the 10 months before and the 10 months after the pandemic were compared and predictors of adequacy were determined.ResultsIn the 388 HD patients included in the study, the number of missed sessions was higher during the pandemic with peaks during the first and second wave of the pandemic. The ratio of patients to nurses, phosphorus and parathormone levels were significantly higher during the pandemic, while urea reduction ratio, Kt/V, hemoglobin, calcium and albumin levels were significantly lower. In patients who reported difficult accessibility, missed HD sessions were higher during lockdown. Hospital admissions doubled during the pandemic, with COVID-19 infection being the main cause (45.5%). Number of patients per nurse and interdialytic weight gain were predictors of inadequate dialysis.ConclusionThe COVID-19 pandemic and its related lockdown negatively affected multiple aspects of dialysis patient care. Continued access of optimum care in dialysis patients should be a priority in any future mass events.

Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Risk factors and outcomes of vitamin D deficiency in very preterm infants

BackgroundVitamin D is essential for bone health and immune system. Vitamin D deficiency (VDD) poses a high-risk to very preterm (VP) infants. This study aimed to evaluate the risk factors associated with VDD in VP infants and its potential clinical outcomes. MethodsA retrospective cohort study was conducted on VP infants admitted to the neonatal intensive care unit of a specialized tertiary hospital in Seoul, Republic of Korea, between January 2018 and June 2022. Serum 25-hydroxyvitamin D (25(OH)D) levels and other biochemical parameters were measured between 4 and 6 weeks of age. VDD was defined as a serum 25(OH)D level <20 ng/mL. Prenatal and postnatal risk factors and clinical outcomes were compared between the VDD and non-VDD groups. ResultsOf the 82 VP infants analyzed, 27 (32.9%) were diagnosed with VDD. The VDD group exhibited a significantly longer duration of parenteral nutrition (PN) compared to the non-VDD group (adjusted odds ratio [OR] = 1.12; 95% confidence interval [CI]: 1.008–1.245). Breast milk intake was lower in the VDD group than in the non-VDD group (adjusted OR = 0.976, 95% CI, 0.955–0.999). Notably, calcium levels were significantly lower in the VDD group, while parathyroid hormone levels were significantly higher, compared with the non-VDD group. Additionally, the rickets severity score was higher in the VDD group than in the non-VDD, although the difference was not statistically significant. ConclusionsProlonged PN duration and low breast milk intake significantly increased the risk of VDD in VP infants.

Disruption of the c-terminal serine protease domain of Fam111a does not alter calcium homeostasis in mice.

FAM111A gene mutations cause Kenney-Caffey syndrome (KCS) and Osteocraniostenosis (OCS), conditions characterized by short stature, low serum ionized calcium (Ca2+), low parathyroid hormone (PTH), and bony abnormalities. The molecular mechanism mediating this phenotype is unknown. The c-terminal domain of FAM111A harbors all the known disease-causing variations and encodes a domain with high homology to serine proteases. However, whether this serine protease domain contributes to the maintenance of Ca2+ homeostasis is not known. We hypothesized the disruption of the serine protease domain of FAM111A would disrupt Ca2+ homeostasis. To test this hypothesis, we generated with CRISPR/Cas9, mice with a frameshift insertion (c.1450insA) or large deletion (c.1253-1464del) mutation in the Fam111a serine protease domain. Serum-ionized Ca2+ and PTH levels were not significantly different between wild type, heterozygous, or homozygous Fam111a mutant mice. Additionally, there were no significant differences in fecal or urine Ca2+ excretion, intestinal Ca2+ absorption or overall Ca2+ balance. Only female homozygous (c.1450insA), but not heterozygous mice displayed differences in bone microarchitecture and mineral density compared to wild-type animals. We conclude that frameshift mutations that disrupt the c-terminal serine protease domain do not induce a KCS or OCS phenotype in mice nor alter Ca2+ homeostasis.

THE COHORT STUDY OF ADIPOCYTES’ SECRETORY ACTIVITY, VITAMIN D, PARATHYROID HORMONE, LEPTIN RESISTANCE AND OBESITY IN HYPERTENSIVE PATIENTS

Objective: Obesity is a major risk factor of essential arterial hypertension (EAH). Therefore, we studied the dependence of 25-OH vitamin D (VitD), parathyroid hormone (PTH), Adiponectine, Leptin and ionized calcium blood values on Obesity degrees in EAH patients. Design and method: Study involves 100 EAH patients with hypertensive-mediated organ damage (moderate-very-high cardiovascular risks, aged 45-65). Obesity was determined by body mass index (BMI) &gt;30 kg/m2: 1st obesity degree – 30-34.9 kg/m2, 2nd – 35-39.9 kg/m2, 3rd – &gt;40 kg/m2. Serum levels of VitD and PTH studied by immunochemiluminescent method, Ca2+– by potentiometric method, Adiponectine and Leptin blood values – by ELISA. Leptin resistance (LR) index calculated by Leptin to Triglycerides Ratio (LTR). Adipocytes Secretory Activity (ASA) calculated by Leptin to BMI Ratio. Results: Adiponectin in EAH with obesity was lower, and leptin, on the contrary, was higher than in EAH without obesity – by 7.54-12.81% (p&lt;0.001) and 1.75-2.63 times (p&lt;0.001) respectively. LR and ASA indexes increased in presence of obesity 1.5-2.2 times (p&lt;0.001) and 1.47-1.85 times (p&lt;0.001), respectively. Adipocytokines concentration depended on the obesity: in 2nd and 3rd degrees EAH patients lower by 5.98% (p&lt;0.001), and leptin, on the contrary, was higher by 50.18% (p&lt;0.001), than in the case of 1st degree obesity, leading to LR and adipocytes’ secretory activity growth by 46.88% (p=0.018) and 26% (p=0.004). In EAH patients with 2nd and 3rd obesity degrees, concentration of 25(OH)VitD was lower by 18.48% (p=0.012), and PTH, was higher by 31.62% (p=0.017), than in obesity-free. Ionized calcium level did not depend on the obesity. Obesity risk in EAH elevated with blood adiponectin decrease (&lt;75ng/ml) by 77 times [OR: 16.25-364.8; p&lt;0.001], leptin augmentation (in women &gt;21 ng/ml, in men &gt;14 ng/ml) – 31 times [OR: 3.93-245.48; p&lt;0.001], LR index increase (&gt;15.0 U) – 5.27 times [OR: 2.04-13.60; p&lt;0.001] and adipocytes’ secretory activity (&gt;0.70 U) – 34.1 times [OR: 4.32-268.7; p&lt;0.001]. Conclusions: Low Adiponectine, Leptin elevation, LR and ASA augmentation increase the obesity risk in EAH 5-77 times (p&lt;0.001). The 2nd and 3rd obesity degrees associate with lower 25(OH)VitD, higher PTH (p&lt;0.05), independetly on ionized calcium.

Role of Leptin in Regulating Renal Phosphate Transport

Elevated plasma phosphate (Pi) levels, known as hyperphosphatemia, are associated with an increased risk of cardiovascular complications and mortality. Although studies have suggested a correlation between obesity and hyperphosphatemia/phosphate toxicity, the root cause of this observation has not been established. Since hyperleptinemia was also found to be associated with abnormalities in bone structure, we hypothesized that effects on renal Pi transport are responsible for this observation. To address this question, we studied hyperleptinemic mice (db/db, n=14) and compared them to wild-type mice (WT, n=10). Blood and urine samples, as well as kidney tissues, were collected and analyzed. Body weight was approximately twice as high in db/db compared to WT mice (59±3 vs. 30±2 g, P&lt;0.05). Plasma Pi levels in db/db mice were significantly greater (~1.5-fold) compared to WT mice (2.6±0.1 vs. 1.7±0.1 mmol/L, P&lt;0.05). However, urinary Pi /creatinine ratios were similar between genotypes. Plasma Ca2+ levels in db/db mice were significantly higher compared to WT mice (2.68±0.03 vs. 2.48±0.03 mmol/L, P&lt;0.05) alongside urinary Ca2+/creatinine ratios being significantly higher in db/db mice compared to WT mice (1.6±0.4 vs. 0.3±0.1 mmol/mmol, P&lt;0.05). Plasma parathyroid hormone (PTH, regulating Pi and Ca2+) levels were similar in both genotypes. The phosphaturic hormone fibroblast growth factor 23 (FGF23), which is produced and released from bone, was slightly but significantly elevated in db/db compared to WT mice (254±12 vs. 227±18 pg/mL, P&lt;0.05). Bone formation markers (osteocalcin and procollagen type I N-propeptide) and bone resorption markers (tartrate-resistant acid phosphatase 5b and C-terminal telopeptide of type I collagen) were similar between genotypes, indicating that Pi and Ca2+ release from bone may not be causing these mineral differences. To determine the role of the kidney for the development of hyperphosphatemia, we performed 32P radiotracer studies in acutely isolated renal brush border membrane vesicles. Sodium-dependent 32P transport was not significantly different between genotypes. To determine the ambient in vivo contribution of the Na+-Pi cotransporter Npt2a, we employed acute pharmacological inhibition with PF-06869206 (Npt2a inhibitor, 30 mg/kg b.w, n=7) or vehicle (n=11) and compared plasma Pi before and 2 hours after administration in db/db mice. Vehicle treatment slightly increased plasma Pi levels compared to baseline (2.6±0.1 vs. 2.1±0.1 mmol/L, P&lt;0.05); in contrast, the Npt2a inhibitor significantly reduced (~50%) plasma Pi levels compared to baseline (1.3±0.1 vs. 2.5±0.1 mmol/L, P&lt;0.05). In summary, our study demonstrates that hyperphosphatemia in db/db mice is not caused by changes in renal Pi transport or bone turnover, suggesting that possibly intestinal mechanisms are responsible for increased Pi, and possibly Ca2+, absorption. Of note, Npt2a inhibition was effective in reducing hyperphosphatemia in db/db mice, indicating a potential therapeutic strategy. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.