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A commonly used method for determining vitamin D sufficiency is the suppression of excess PTH secretion. Conventionally, the main circulating vitamin D metabolite 25(OH)D is used for this assessment, however, the cut-off data for this parameter vary widely in the literature. The role of other metabolites as markers of vitamin D status is actively debated. The aim of our study was to assess the relationship between PTH, age and parameters characterizing vitamin D status, both "classical" - 25(OH)D3, and "non-classical" - 24,25(OH)2D3 and 25(OH)D3/24,25(OH)2D3 (vitamin D metabolite ratio, VMR). This prospective non-controlled cohort study included 162 apparently healthy Caucasian adult volunteers. When PTH was binarized according to the median value, at VMR < 14.9, 25(OH)D3 > 9.7 ng/mL and 24,25(OH)2D3 > 0.64 ng/mL there was a pronounced relationship between PTH and age (p = 0.001, p = 0.023 and p = 0.0134 respectively), with the prevalence of higher PTH levels in older individuals and vice versa. Moreover, at an age of <40.3 years, there was a pronounced relationship between PTH and VMR (p < 0.001), and similarly at an age of <54.5 years, there was a pronounced relationship between PTH and 25(OH)D3 (p = 0.002) as well as between PTH and 24,25(OH)2D3 (p = 0.0038): in younger people, higher PTH values prevailed only in the range of vitamin D insufficiency, while in the older age group this relationship was not demonstrated and PTH values were in general above the median. VMR controlled the correlation between PTH and age more strongly than metabolites 25(OH)D3 and 24,25(OH)2D3 (p = 0.0012 vs. p > 0.05 and p = 0.0385 respectively). The optimal threshold was found equal to 11.7 for VMR such that the relationship between PTH and age in the subset of participants with VMR < 11.7 was characterized by a correlation coefficient of ρ = 0.68 (p < 0.001), while the cohort with VMR > 11.7 was characterized by a very weak correlation coefficient of ρ = 0.12 (p = 0.218), which is non-significant. In summary, our findings suggest that the relationship between PTH and vitamin D is age-dependent, with a greater susceptibility to elevated PTH among older individuals even with preserved renal function, likely due to the resistance to vitamin D function. We propose VMR can be considered as a potential marker of vitamin D status. These findings require confirmation in larger population-based studies.

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The concomitant occurrence of renal cell carcinoma (RCC) and primary hyperparathyroidism is rare as these conditions are often identified by the presence of hypercalcemia, which might be missed in asymptomatic individuals. We present the case of a 58-year-old asymptomatic male detected to have a left abdominal mass during his routine medical follow-up. He was subsequently diagnosed with RCC. Further history revealed that his calcium levels had been persistently elevated for the past eight years but had never been investigated. Based on elevated parathyroid hormone levels and radiological findings, a diagnosis of primary hyperparathyroidism has also been made. A right inferior parathyroidectomy was performed, and the histopathological examination results showed a right parathyroid adenoma. Intraoperative intact PTH (iPTH) measurements confirmed the complete removal of the abnormal parathyroid gland. The postoperative calcium levels have returned to normal. To the best of our knowledge, this was the first reported case of concurrent primary hyperparathyroidism and RCC in our population. This case illustrates the importance of considering a broad differential when evaluating patients with hypercalcemia.

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Diagnosing primary hyperparathyroidism in pregnancy is difficult due to pregnancy-related changes in parathyroid hormone (PTH); calcium; 1,25 vitamin D; and renal calcium excretion. Parathyroid hormone-related peptide (PTHrP) produced by the placenta adds additional complexity. Our case is the first to demonstrate an increased rate of PTH degradation within a pregnant individual who returned unexpectedly low PTH levels. We describe a 27-year-old female patient who presented at 25 weeks gestation with pancreatitis and hypercalcemia. Primary hyperparathyroidism was suspected but variable PTH results led to uncertainty and an assay error was considered. PTH samples were collected in both serum-separating tubes (SST) and EDTA tubes and compared to controls (5 nonpregnant and 5 pregnant individuals). Samples were retested every 2 hours for a period of 10 hours. A rapid decline in the measured PTH was noted in the index case, an observation which differed from controls. We postulated that internal and/or external factors influenced the PTH measurement obtained from our patient. From our observations, rapid PTH degradation in pregnancy, and individual variation in PTH stability and laboratory processes, can influence PTH results and impact on interpreting hypercalcemia in pregnancy.

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We report two patients of east African ancestry with the same novel homozygous variant in the parathyroid hormone receptor type 1 (PTH1R). Both patients shared skeletal features including brachydactyly, extensive metacarpal pseudoepiphyses, elongated cone-shaped epiphyses, ischiopubic hypoplasia, deficient sacral ossification, suggestive of Eiken syndrome. Strikingly, both patients exhibited clinically manifest parathyroid hormone (PTH) resistance with hypocalcaemia and elevated serum phosphate levels. These laboratory and clinical abnormalities initially suggested pseudohypoparathyroidism, which is typically associated with GNAS abnormalities. In both patients, however, a homozygous novel PTH1R variant was identified (c.710 T > A; p.IIe237Asn, p.I237N) that is located in the second transmembrane helical domain. Previously, others have reported a patient with a nearby PTH1R mutation (D241E) who presented with similar clinical features, e.g. delayed bone mineralization as well as clinical PTH resistance. Functional analysis of the effects of both novel PTH1R variants (I237N- and D241E-PTH1R) in HEK293 reporter cells transfected with plasmid DNA encoding the wild-type or mutant PTH1Rs demonstrated increased basal cAMP signalling for both variants, with relative blunting of responses to both PTH and PTH-related peptide (PTHrP) ligands. The clinical presentation of PTH resistance and delayed bone mineralization combined with the functional properties of the mutant PTH1Rs suggest that this form of Eiken syndrome results from alterations in PTH1R-mediated signalling in response to both canonical ligands, PTH and PTHrP.

Eiken syndrome is an extremely rare genetic disorder of skeletal development, previously reported in only 7 people in the medical literature. It is due to alterations in the gene for the parathyroid hormone receptor type 1 (PTH1R). This receptor can bind two different hormones; parathyroid hormone (PTH), which is the body's main regulator of the level of calcium in the blood, and parathyroid hormone related peptide (PTHrP), a smaller hormone that regulates bone development. We report two new cases of Eiken syndrome sharing the exact same change in the PTH1R gene. This genetic change has not been previously reported. The patients had many of the typical findings in the skeleton reported in previous cases of Eiken syndrome, but with some variation in the features. However, unlike any previously reported people with Eiken syndrome, the two patients we describe had low levels of calcium in the blood causing significant symptoms. Low calcium has been reported in some cases of Eiken syndrome before, but this has been mild and not associated with symptoms. We wanted to explore how this new mutation affects the function of the PTH receptor, particularly how it might affect the signals generated when the receptor binds to its two different hormones, PTH and PTHrP. We did this by genetically reprogramming a cell line with the new mutation, and then testing those cells' responses to stimulation by the two hormones. We showed that the altered receptor appears to be unable to bind both hormones in a stable fashion, explaining why the patients showed changes both in the skeleton (due mostly to altered PTHrP signalling) and in the blood level of calcium (mostly due to altered PTH signalling).

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COVID-19 can lead to various complications, including severe respiratory symptoms. Both viral infections and total thyroidectomy are known to cause hypocalcemia, making a history of thyroidectomy a potential risk factor for hypocalcemia in COVID-19 patients. We present the case of a 34-year-old woman with Graves' disease who developed hypocalcemia due to COVID-19 following a total thyroidectomy. The patient underwent an uneventful total thyroidectomy, with preservation of at least three of the four parathyroid glands. Postoperatively, her parathyroid hormone (PTH) levels were normal, and she was discharged without tetany. However, on postoperative day 90, she experienced mild hypocalcemia during a COVID-19 infection, although it was asymptomatic. By postoperative day 127, she presented with severe tetany and general malaise. Testing confirmed a reinfection with SARS-CoV-2 and hypocalcemia, while PTH levels remained normal. Treatment with intravenous calcium gluconate, oral calcium lactate, and alfacalcidol effectively resolved the hypocalcemia and tetany. The patient was subsequently discharged without tetany and has since been monitored without the need for calcium or vitamin D supplementation. This case highlights that the COVID-19 infection following a total thyroidectomy can cause hypocalcemia. Postoperative hypocalcemia is a common issue in head and neck surgery, and viral infections like COVID-19 should be considered in the differential diagnosis of hypocalcemia.

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Aim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations. Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations. Results: We found that gender were associated with 25(OH)D, OC, ß-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P<0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in ß- CTX levels between seasons. Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.

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Regardless of species, calcium, vitamin D, and parathyroid hormone physiology are intricately linked. However, there are many unique differences between taxa that may affect husbandry recommendations, common disease processes, and effective treatment. This article aims to provide a basic overview of calcium metabolism and physiology then specifically delve into unique attributes of calcium homeostasis in common zoologic companion animal species.

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OBJECTIVE: The prevalence of type 2 diabetes mellitus (T2DM) and bone metabolism disorders increase with age. Diabetic kidney disease (DKD) is one of the most serious microvascular complications of T2DM, and bone metabolism disorders are closely linked to the occurrence of DKD. The relationship between bone turnover markers(BTMs) and the kidney disease in elderly patients with T2DM remains unclear. Therefore, this study aims to investigate the association between common BTMs and DKD in a large sample of elderly patients. The goal is to provide a basis for early identification of high-risk individuals for DKD among elderly T2DM patients from a bone metabolism perspective. METHODS: In this cross-sectional study, BTMs were collected from a cohort of 2,051 hospitalized Chinese patients. The relationships between 25-hydroxyvitamin D (25-OH-D), ß-CrossLaps (ß-CTX), osteocalcin (OSTEOC), intact parathyroid hormone (iPTH), and total type I collagen N-terminal propeptide (TP1NP), and DKD, as well as urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were analyzed using regression analysis and restrictive cubic spline (RCS) curves. RESULTS: Higher 25-OH-D levels were independently linked to a lower incidence of DKD and decreased UACR. The RCS curves showed a linear association of 25-OH-D and DKD, approaching the L-shape. ß-CTX was independently and positively correlated with UACR. There is an independent positive correlation between OSTEOC and UACR and a negative correlation with eGFR. iPTH is independently and positively correlated with DKD incidence and UACR, and negatively correlated with eGFR. Additionally, the RCS curves showed a non-linear association of OSTEOC and iPTH and DKD, approaching the J-shape, and the point of inflection is 10.875 ng/L and 34.15 pg/mL respectively. There is an independent positive correlation between TP1NP and UACR incidence, and a negative correlation with eGFR. Risk estimates significantly increase with higher TP1NP levels in the RCS model. CONCLUSION: BTMs are closely associated with kidney disease in elderly patients with T2DM. These discoveries potentially assist clinicians in establishing more preventive measures and targeted treatment strategies for elderly patients with T2DM.

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Objective: The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. Methods: A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1-34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Results: Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01-0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00-0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1-34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32-2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45-0.072), with no significant difference observed in mortality rates between treatment and control groups. Conclusion: Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

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Hypercalcemia is a significant complication in cancer patients, primarily caused by parathyroid hormone-related peptide (PTHrP) and, rarely, by parathyroid hormone (PTH) production from tumors. We report a case of severe hypercalcemia in a woman with uterine cancer who exhibited elevated PTH and PTHrP levels. Surgical intervention revealed dedifferentiated endometrial carcinoma. Postoperatively, PTH and PTHrP levels normalized but subsequently increased due to metastases. A molecular analysis confirmed the expression of the PTH gene and protein within the tumor, indicating ectopic PTH production. In diagnosing and treating cancers, it is necessary to consider not only PTHrP production but also ectopic PTH production.

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Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia. It is secondary to hypersecretion of parathyroid hormone (PTH) by the parathyroid glands. Today, PHTP is asymptomatic in 80-90% of cases. Its repercussions are mainly renal (nephrolithiasis, nephrocalcinosis, decline in renal function) and skeletal (osteoporosis, fractures), and should be systematically investigated. Diagnosis is only biological, and in its classic form relies on the association of hypercalcemia, inappropriate PTH (normal or elevated) and hypercalciuria. Diagnosis of normocalcemic forms, where only PTH is elevated, requires elimination of secondary hyperparathyroidism and confirmation of elevated PTH on two consecutive samples, over a 3 to 6 months period. Imaging evaluation, which combines neck ultrasound with scintigraphy or 18F-choline PET/CT, is of interest only if surgery is indicated. Surgical management of the hyperfunctioning parathyroid gland(s) is the only curative treatment for HPTP. Medical management concerns patients for whom surgery is not indicated, who present a surgical contraindication or who refuse surgery. The diagnosis of HPTP warrants contact with an endocrinologist to ensure its management.

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Abnormal mechanical loading is one of the major risk factors for articular cartilage degeneration. Engineered mesenchymal stromal cell (MSC)-derived cartilage holds great promise for cell-based cartilage repair. However, physiological loading protocols were shown to reduce matrix synthesis of MSC-derived neocartilage in vitro and the regulators of this undesired mechanoresponse remain poorly understood. Parathyroid hormone-related protein (PTHrP) is involved in cartilage development and can affect extracellular matrix (ECM) production during MSC chondrogenesis opposingly, depending on a continuous or transient exposure. PTHrP is induced by various mechanical cues in multiple tissues and species; but whether PTHrP is regulated in response to loading of human engineered neocartilage and may affect matrix synthesis in a positive or negative manner is unknown. The aim of this study was to investigate whether dynamic loading adjusts PTHrP-signaling in human MSC-derived neocartilage and whether it regulates matrix synthesis and other factors involved in the MSC mechanoresponse. Interestingly, MSC-derived chondrocytes significantly upregulated PTHrP mRNA (PTHLH) expression along with its second messenger cAMP in response to loading in our custom-built bioreactor. Exogenous PTHrP(1-34) induced the expression of known mechanoresponse genes (FOS, FOSB, BMP6) and significantly decreased glycosaminoglycan (GAG) and collagen synthesis similar to loading. The adenylate-cyclase inhibitor MDL-12,330A rescued the load-mediated decrease in GAG synthesis, indicating a direct involvement of cAMP-signaling in the reduction of ECM production. According to COL2A1-corrected hypertrophy-associated marker expression, load and PTHrP treatment shared the ability to reduce expression of MEF2C and PTH1R. In conclusion, the data demonstrate a significant mechanoinduction of PTHLH and a negative contribution of the PTHrP-cAMP signaling axis to GAG synthesis in MSC-derived chondrocytes after loading. To improve ECM synthesis and the mechanocompetence of load-exposed neocartilage, inhibition of PTHrP activity should be considered for MSC-based cartilage regeneration strategies.

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BACKGROUND: A defective synthesis of vitamin D contributes to alterations in calcium homeostasis due to chronic endocrinopathies, leading to metabolic bone diseases. This study aimed to ascertain the levels of calcium, vitamin D, and parathyroid hormone (PTH) in children with ß-thalassemia. METHODS: In this case-control study, 36 children with major ß-thalassemia receiving iron chelation therapy were included. For the control group, 36 cases matched for age and sex were selected. The packed cell volume (PCV) requirements varied among the thalassemic children, with an average PCV requirement of 78.57±49.07. The study was conducted for six months in the Department of Pediatrics at the Government Medical College, Nagpur, India. Serum PTH levels were determined by immunoassay, and serum vitamin D levels were assessed using electrochemiluminescence technique. Additional tests looked at liver function, serum ferritin, calcium, phosphorus, and complete blood count. The student's t-test, Mann-Whitney, and chi-square tests were used for statistical analysis. RESULT: In comparison to the control group (10.4±1.21 g/dL), the case group's mean hemoglobin level was considerably lower (5.62±1.9 g/dL) (p<0.001). The mean serum ferritin level in the cases was notably higher (3073±1262.24 ng/mL) compared to the control group's level (58.37±29.67 ng/mL) (p<0.001). A total of 80.6% of cases compared to 5.6% of controls had vitamin D deficiency, and 72.2% of cases compared to 2.8% of controls had PTH deficit, both of which showed statistically significant differences (p<0.001). Significant differences were observed between the case and control groups for the mean levels of total serum calcium (8.51±0.84 mg/dL), vitamin D (15.23±10.07 ng/mL), and PTH (14.66±19.86 pg/mL) (9.13±0.6 mg/dL, p=0.05; 34.94±9.57 ng/mL, p<0.001; 32.08±12.42 pg/mL, p<0.001; respectively). CONCLUSION: Growth failure may result from the markedly reduced serum calcium, vitamin D, and PTH levels in children with ß-thalassemia. The relevance of treatment approaches is highlighted by the possibility that these anomalies are caused by excessive iron and inadequate nutritional support.

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PURPOSE: Parathyroid hormone (PTH) is merit as a risk factor for mortality in patients with chronic kidney disease in prevalent hemodialysis patients in a U shape. Most studies, however, do not focus on incident patients and those who died within the first 90 days of therapy. We evaluated PTH as a risk factor for mortality in a large cohort population in Brazil. METHODS: This is an observational cohort study that included 4317 adult patients who initiated hemodialysis between July 1st, 2012 and June 30, 2017. The main outcome was all-cause mortality. Fine-gray sub-distribution hazard models were used to evaluate survival in the presence of a competing event (kidney transplant). RESULTS: Median PTH levels of 252 (118, 479) pg/mL. There were 331 deaths during the first 90 days of therapy (6.7%), 430 in a 1-year follow-up (10.7%) and 1282 (32%) during the 5-year study period. Deaths according to PTH < 150, 150-600 and > 600 pg/mL corresponded to 38.1%, 33.0% and 28.5%, respectively (p < 0.001). In an adjusted model, patients who started dialysis with PTH < 150 pg/mL had a higher mortality risk within the first 90 days, but not in 1 year and 5 years after starting dialysis. Analyses in a subset of patients with a repeated PTH in 1 year (N = 1954) showed that although persistent PTH low levels (< 150 pg/mL) at 1 year were significantly associated with all-cause mortality, this result was not sustained after multiple adjustments. CONCLUSION: PTH < 150 pg/mL confers a high mortality risk in the first 90 days of dialysis. If this result reflects poor nutritional conditions, it deserves further investigations.

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INTRODUCTION: Chronic kidney disease (CKD) and its associated complications, such as anemia and secondary hyperparathyroidism (SHPT), pose significant challenges to global healthcare systems. This study explores the demographic and clinical characteristics of 284 kidney failure (KF) patients undergoing hemodialysis, in an effort to shed light on the possible association between anemia and SHPT. A proven connection between the two could theoretically influence the management plans for CKD patients, with the hopes of achieving lower morbidity and/or mortality in this patient group. METHODS: A retrospective, cross-sectional, real-world data analytical study was conducted at a hemodialysis center in Tbilisi, Georgia, encompassing a sample size of n = 284 patients on maintenance hemodialysis. The data analyzed was extracted from patients' medical records. RESULTS: According to our results, the prevalence of anemia was strikingly high at 82.04%, underlining its substantial burden within this patient population. Our analysis revealed a notable systemic association between anemia and SHPT, particularly when considering hemodialysis vintage. However, our final analysis model revealed no statistically significant association between anemia and intact parathyroid hormone (iPTH) levels.  Conclusion: Our study revealed a significant systemic relationship between anemia and SHPT when hemodialysis duration was considered, despite initial analyses showing no direct association. Future research should focus on longitudinal and multi-center studies to better understand this relationship, aiming to enhance the care and management of CKD patients on hemodialysis.

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OBJECTIVES: The aim of this study was to determine the disturbances in the concentration of parathyroid hormone (PTH) and 25-hydroxyvitamin D (vitamin D) in patients with stable chronic obstructive pulmonary disease (COPD) and its correlation with airflow obstruction. MATERIALS AND METHODS: A prospective study included 200 patients with a confirmed diagnosis of COPD in the Department of Lung Diseases and Tuberculosis and Pulmonology Polyclinic of University Clinical Hospital Mostar in the period of three years, between May 2021 and May 2024. Inclusion criteria were a stable phase of COPD, hemodynamically stable patients older than 40 years, forced vital capacities in the first second (FEV1)/forced vital capacities (FVC) <0.7, and patients with PTH, vitamin D, calcium, and phosphate measurements. Exclusion criteria were acute exacerbation of COPD in the last month; current treatment with nutritional supplements, vitamins, and statins; lack of availability of lung function data; use of systemic corticosteroids in the previous three months; chronic renal insufficiency, respiratory diseases other than COPD (asthma, pneumonia, tuberculosis, and bronchiectasis), and other diseases (cancer and parathyroid disease). Medical records about demographic data (age and gender), pulmonary function test (FVC, FEV1, FEV1%FVC, mean expiratory flow (MEF)50), body mass index (BMI), COPD assessment test (CAT), Modified Medical Research Council (mMRC) Dyspnea Scale, and serum PTH, vitamin D, calcium, and phosphate levels were obtained. RESULTS:  Patients with higher COPD stage had lower spirometry values, most significantly MEF50. The higher the COPD group (Global Initiative for Chronic Obstructive Lung Disease (GOLD) D), the lower vitamin D ​​and the higher PTH levels were. Calcium and phosphate values ​​were the same for all groups. Vitamin D and PTH levels significantly ​​correlated with MEF50 values. The lower MEF50 level, the higher PTH levels, ​​and lower vitamin D levels were found (P<0.05). CONCLUSION: Our study showed that the patients in the higher COPD group have lower vitamin D levels ​​and higher PTH levels, indicating that they developed secondary hyperparathyroidism. The levels of vitamin D and PTH correlated the most with MEF50 values while other spirometry parameters did not significantly correlate with vitamin D and PTH levels.

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BACKGROUND: Vitamin D may prevent the development of hypertension through down-regulation of renin-angiotensin system. However, epidemiologic studies assessing the interrelation of vitamin D-related biomarkers with hypertension are sparse. METHODS: We examined the prospective associations between vitamin D-related biomarkers and risk of hypertension in a nested case-control study. In each of the Women's Health Study (WHS) and Physicians' Health Study (PHS) II, 500 incident hypertension cases and 500 age and race matched controls were randomly selected. Baseline plasma 25(OH)-vitamin D [25(OH)D], parathyroid hormone (PTH), and total renin concentrations were measured. RESULTS: Among controls, 25(OH)D and PTH were inversely correlated, but neither was correlated with total renin. In the crude model, there was a trend of association between increasing quintiles of 25(OH)D and lower risk of hypertension in women, with relative risks and 95% CIs of 1.00, 1.24 (0.84-1.83), 0.82 (0.53-1.25), 0.75 (0.48-1.16), and 0.81 (0.52-1.27) (p, trend: 0.07). Adjustment for body mass index and other hypertension risk factors eliminated this association (RR of 5th quintile: 1.03). No associations were found in men. Baseline PTH and ratio of 25(OH)D to PTH were not associated with risk of hypertension in women or men. When men and women were included in the same model, vitamin D insufficiency (defined as 25(OH)D <20 ng/mL) also was not associated with increased risk of hypertension. No interactions were found across subgroups. CONCLUSIONS: Our study found no association of baseline plasma 25(OH)D or PTH with risk of hypertension or total renin concentration in middle-aged and older men and women.

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Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD. Methods: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH. Results: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients. Conclusion: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients.

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Introduction. Hypercalcemia is infrequent in pediatrics, of diverse etiology, and with multiorgan morbidity. Objective. Describe the etiology, biochemistry, clinical, and treatment in pediatric patients with hypercalcemia. Population and methods. Retrospective and descriptive study of a cohort of patients with hypercalcemia between 2008 and 2022. They were classified into three groups (G): hypercalcemia of iatrogenic cause (G1), parathyroid hormone (PTH) independent (G2), or PTH-dependent (G3). Results. One hundred forty-seven patients were included; 57% were male, with a median age of 3.7 years, median calcemia of 11.8 mg/dl, and mean phosphatemia of 4.9 mg/dl. Symptoms were present in 29% of patients, and 28.6% required additional treatments to those of the first line. In G1, 76 patients (51.7%) were included; in G2, 58 (39.4%), and in G3, 13 (8.8%). Median calcemia was lower in G1 vs. G2 and G3 (11.6 mg/dl, 12.6 mg/dl, and 12.3 mg/dl), and mean phosphatemia was lower in G3 vs. G1 and G2 (3.7 mg/dl, 5.3 mg/dl, and 4.9 mg/dl). Most of the patients with hypercalcemia were asymptomatic and did not require additional treatments. The percentage of symptomatic patients and the percentage requiring additional treatment were lower in G1 than in the other two groups. Conclusions. Iatrogenesis was the most frequent cause, presenting lower calcemia, while PTH-dependent causes presented the lowest phosphatemia. PTH-independent causes represented a diagnostic and therapeutic challenge due to lacking a characteristic biochemical profile.

Introducción. La hipercalcemia es infrecuente en pediatría, de etiología diversa y con morbilidad multiorgánica. Objetivo. Describir etiología, bioquímica, clínica y tratamiento en pacientes pediátricos con hipercalcemia. Población y métodos. Estudio retrospectivo y descriptivo de una cohorte de pacientes con hipercalcemia entre 2008 y 2022. Se clasificaron en tres grupos (G): hipercalcemia de causa iatrogénica (G1), paratohormona (PTH) independiente (G2) o PTH dependiente (G3). Resultados. Se incluyeron 147 pacientes; el 57 % eran varones, edad mediana de 3,7 años, calcemia mediana 11,8 mg/dl y fosfatemia media 4,9 mg/dl. El 29,9 % de los pacientes fueron sintomáticos y el 28,6 % requirió tratamientos adicionales a los de la primera línea. En G1 se incluyeron 76 pacientes (51,7 %); en G2, 58 (39,4 %), y en G3, 13 (8,8 %). La calcemia mediana fue menor en G1 vs. G2 y G3 (11,6 mg/dl, 12,6 mg/dl y 12,3 mg/dl). La fosfatemia media fue menor en G3 vs. G1 y G2 (3,7 mg/dl, 5,3 mg/dl y 4,9 mg/dl). La mayoría de los pacientes con hipercalcemia fueron asintomáticos sin requerimientos de tratamientos adicionales. El porcentaje de pacientes sintomáticos y el de requerimiento de tratamientos adicionales fue menor en G1 que en los otros dos grupos. Conclusiones. La iatrogenia fue la causa más frecuente, y se presentó con calcemias más bajas; mientras que las causas PTH dependientes presentaron las fosfatemias más bajas. Las causas PTH independientes representaron un desafío diagnóstico y terapéutico por la falta de un perfil bioquímico característico.

RESUMEN

The sodium/proton exchanger-3 (NHE3) plays a major role in acid-base and extracellular volume regulation and is also implicated in calcium homeostasis. As calcium and phosphate balances are closely linked, we hypothesized that there was a functional link between kidney NHE3 activity, calcium, and phosphate balance. Therefore, we examined calcium and phosphate homeostasis in kidney tubule-specific NHE3 knockout mice (NHE3loxloxPax8 mice). Compared to controls, these knockout mice were normocalcemic with no significant difference in urinary calcium excretion or parathyroid hormone levels. Thiazide-induced hypocalciuria was less pronounced in the knockout mice, in line with impaired proximal tubule calcium transport. Knockout mice had greater furosemide-induced calciuresis and distal tubule calcium transport pathways were enhanced. Despite lower levels of the sodium/phosphate cotransporters (NaPi)-2a and -2c, knockout mice had normal plasma phosphate, sodium-dependent 32Phosphate uptake in proximal tubule membrane vesicles and urinary phosphate excretion. Intestinal phosphate uptake was unchanged. Low dietary phosphate reduced parathyroid hormone levels and increased NaPi-2a and -2c abundances in both genotypes, but NaPi-2c levels remained lower in the knockout mice. Gene expression profiling suggested proximal tubule remodeling in the knockout mice. Acutely, indirect NHE3 inhibition using the SGLT2 inhibitor empagliflozin did not affect urinary calcium and phosphate excretion. No differences in femoral bone density or architecture were detectable in the knockout mice. Thus, a role for kidney NHE3 in calcium homeostasis can be unraveled by diuretics, but NHE3 deletion in the kidneys has no major effects on overall calcium and phosphate homeostasis due, at least in part, to compensating mechanisms.