Characterization of a cohort of patients with hypercalcemia in a tertiary pediatric hospital. / Caracterización de una cohorte de pacientes con hipercalcemia en un centro pediátrico de tercer nivel.

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.

Associations Of Vitamin D-Related Biomarkers With Hypertension And The Renin-Angiotensin System In Men And Women.

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.

Residential Greenness, Lifestyle, and Vitamin D: A Longitudinal Cohort of South Asian Origin and Caucasian Ethnicity Women Living in the South of the UK.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim of this study was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women living at latitude 51°14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant's home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13-2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44-2.92). Our results provide an insight into the connection between residential greenness, lifestyle, and vitamin D status comparing two ethnicities in a country with a temperate climate and with a high degree of urbanization.

Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Assessing Symptomatic Hypocalcemia Risk After Total Thyroidectomy: A Prospective Study.

Introduction The most common postoperative complication of total thyroidectomy is hypocalcemia, usually monitored using serum parathyroid hormone and calcium values. Objective To identify the most accurate predictors of hypocalcemia, construct a risk assesment algorithm and analyze the impact of using several calcium correction formulas in practice. Methods A prospective, single-center, non-randomized longitudinal cohort study on 205 patients undergoing total thyroidectomy. Parathyroid hormone, serum, and ionized calcium were sampled post-surgery, with the presence of symptomatic or laboratory-verified asymptomatic hypocalcemia designated as primary outcome measures. Results Parathyroid hormone sampled on the first postoperative day was the most sensitive predictor of symptomatic hypocalcemia development (sensitivity 80.22%, cut-off value ≤2.03 pmol/L). A combination of serum calcium and parathyroid concentration sampled on the first postoperative day predicted the development of hypocalcemia during recovery with the highest sensitivity and specificity (94% sensitivity, cut-off ≤2.1 mmol/L, and 89% specificity, cut-off ≤1.55 pmol/L, respectively). The use of algorithms and correction formulas did not improve the accuracy of predicting symptomatic or asymptomatic hypocalcemia. Conclusions The most sensitive predictor of symptomatic hypocalcemia present on the fifth postoperative day was PTH sampled on the first postoperative day. The need for algorithms and correction formulas is limited.

Development of a tool to calculate the probability of hypocalcemia after total thyroidectomy: a prospective study.

PURPOSE: This study aimed to evaluate the ability of the percentage of decrease in serum PTH level in the first 8 h after total thyroidectomy (TT) to predict hypocalcemia requiring Ca supplementation and develop a tool to predict it. METHODS: 97 patients who underwent TT with measurement of preoperative parathyroid hormone (PTH) levels were prospectively evaluated 1 and 8 h after TT; postoperative magnesium (Mg2PO) and phosphorus levels were evaluated on the 2nd day after surgery. The percentage of decrease in PTH level 1 h (%dPTH1h) and 8 h (%dPTH8h) postoperatively and predictors of hypocalcemia requiring Ca supplementation were evaluated and an equation was developed to predict this outcome. RESULTS: %dPTH1h (p = 0.002), %dPTH8h (p = 0.001) and (Mg2PO) (p < 0.01) were isolated predictors of postoperative hypocalcemia requiring Ca supplementation. The data obtained led to the development of two tools to predict this complication. CONCLUSIONS: The percentage of decrease in PTH level 1 h and 8 h postoperatively and the magnesium level on the 2nd day after surgery were predictors of more severe hypocalcemia, and an auxiliary tool for predicting this complication was developed.

Assessing Symptomatic Hypocalcemia Risk After Total Thyroidectomy: A Prospective Study

Abstract Introduction The most common postoperative complication of total thyroidectomy is hypocalcemia, usually monitored using serum parathyroid hormone and calcium values. Objective To identify the most accurate predictors of hypocalcemia, construct a risk assesment algorithm and analyze the impact of using several calcium correction formulas in practice. Methods A prospective, single-center, non-randomized longitudinal cohort study on 205 patients undergoing total thyroidectomy. Parathyroid hormone, serum, and ionized calcium were sampled post-surgery, with the presence of symptomatic or laboratory-verified asymptomatic hypocalcemia designated as primary outcome measures. Results Parathyroid hormone sampled on the first postoperative day was the most sensitive predictor of symptomatic hypocalcemia development (sensitivity 80.22%, cut-off value ≤ 2.03 pmol/L). A combination of serum calcium and parathyroid concentration sampled on the first postoperative day predicted the development of hypocalcemia during recovery with the highest sensitivity and specificity (94% sensitivity, cut-off ≤2.1 mmol/L, and 89% specificity, cut-off ≤1.55 pmol/L, respectively). The use of algorithms and correction formulas did not improve the accuracy of predicting symptomatic or asymptomatic hypocalcemia. Conclusions The most sensitive predictor of symptomatic hypocalcemia present on the fifth postoperative day was PTH sampled on the first postoperative day. The need for algorithms and correction formulas is limited.

Association of defects of enamel with polymorphisms in the vitamin D receptor and parathyroid hormone genes

Abstract This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.

Resumo Este estudo transversal teve como objetivo investigar a associação entre defeitos de desenvolvimento do esmalte (DDE) e polimorfismos de nucleotídeo único (SNPs) nos genes que codificam o receptor da vitamina D (VDR) e o hormônio da paratireoide (PTH). Pacientes ortodônticos em tratamento em uma escola Odontologia foram selecionados por amostragem de conveniência. Os DDEs foram avaliados e classificados por um examinador calibrado (Kappa>0,80) através de fotografias intraorais de acordo com os critérios propostos por Ghanim et al. (2015). Os tipos de DDE considerados para análise foram: hipoplasia de esmalte, hipomineralização molar-incisivo (HMI), hipomineralização de segundos molares decíduos (HSMD) e opacidades demarcadas não-HMI/HSMD. O DNA gnômico foi extraído de células bucais. Os SNPs em VDR (rs7975232) e PTH (rs694, rs6256 e rs307247) foram genotipados por PCR em tempo real. As análises estatísticas foram realizadas utilizando o software PLINK (versão 1.03, concebido por Shaun Purcell, EUA). Foram feitos teste de qui-quadrado e teste exato de Fisher com um nível de significância de 5%. Foram incluídos noventa e um (n=91) pacientes (49 do sexo feminino e 42 do sexo masculino) (idade média de 14,1±5,8 anos). A frequência de DDE foi de 38,5% (35 pacientes). As distribuições genotípicas estavam em equilíbrio de Hardy-Weinberg. Não foi encontrada associação estatisticamente significante entre os DDEs e os SNPs avaliados. Foi observada uma associação limítrofe (p=0,09) entre a DDE e o haplótipo CC para o SNP rs7975232 no VDR. Em conclusão, os SNPs seleccionados nos genes VDR e PTH não foram associados à DDE nas amostras estudadas.

Relación entre hormona paratiroidea alterada y fracturas óseas en pacientes en hemodiálisis

Contexto: Las fracturas óseas en pacientes en hemodiálisis son frecuentes y agregan una grave incapacidad y morbimortalidad; se han relacionado a alteraciones óseo-minerales, aunque su asociación con las alteraciones de la hormona paratiroidea es controversial. Objetivo: determinar la relación entre hormona paratiroidea intacta (PTH) alterada y fracturas óseas en pacientes en hemodiálisis. Metodología: se realizó un estudio transversal y analítico en 250 pacientes en hemodiálisis atendidos en el Hospital Víctor Lazarte Echegaray (La Libertad, Perú) entre el 2015 y el 2020. Los pacientes se clasificaron de acuerdo con su valor de PTH (alterada si PTH 300 pg/ml) y la presentación de fracturas óseas. La asociación entre PTH alterada y la presencia de fracturas óseas se determinó al usar un análisis bivariado y multivariado; los resultados se presentan como odds ratio (OR) considerando un valor p significativo si < 0,05. Resultados: se evaluaron 250 pacientes, 69 tuvieron PTH alterada (27,6 %) y 181 tuvieron PTH normal (72,4 %); asimismo, 42 tenían fracturas óseas (16,8 %) y 208 no tenían fracturas óseas (83,2 %). De los 42 pacientes con fracturas óseas, 22 presentaron PTH alterada (52,4 %) y 20 PTH normal (47,6 %); de los 208 pacientes sin fracturas óseas, 47 presentaron PTH alterada (22,6 %) y 161 PTH normal (p = 0,001) (77,4 %). Así, tener PTH alterada se asoció a la presencia de fracturas óseas con un OR de 3,77 (IC 95 %: 1,90-7,49) en el análisis bivariado y un OR de 2,85 (IC 95 %: 1,19-6,82) en el análisis multivariado. Las covariables que se asociaron a presencia de fracturas óseas fueron: tener más de 60 años (OR: 2,74, IC 95 %: 1,12-6,69) y tener más de cinco años en hemodiálisis (OR: 6,72, IC 95 %: 2,98-15,13). Conclusiones: la hormona paratiroidea alterada se relaciona con fracturas óseas en pacientes en hemodiálisis.

Background: Bone fractures in patients on dialysis are frequent and impose a high burden of disability and multimorbidity. They have been linked to mineral-bone disorders but its association with parathyroid hormone remains controversial. Purpose: To determine the relationship between altered parathyroid hormone (PTH) and bone fractures in hemodialysis patients. Metthodology: A cross-sectional, analytical study was conducted in 250 hemodialysis patients attending Hospital Víctor Lazarte Echegaray from 2015 to 2020. Patients were classified according to whether their PTH was altered (PTH 300 pg/ml) and whether bone fractures were present. The association between altered PTH and the presence of bone fractures was determined using bivariate and multivariate analysis; the results are presented as odds ratio (OR) considering a significant p-value if <0.05. Results: 250 patients were evaluated in which 69 (27.6%) had altered PTH, 181 (72.4%) had normal PTH; likewise, 42 (16.8%) had bone fractures and 208 (83.2%) had no bone fractures. Of the 42 patients with bone fractures, 22 (52.4%) had altered PTH and 20 (47.6%) had normal PTH; of the 208 patients without bone fractures, 47 (22.6%) had altered PTH and 161 (77.4%) had normal PTH (p=0.001). Altered PTH was associated with the presence of bone fractures with OR: 3.77 (95% CI: 1.90-7.49) in the bivariate analysis and with OR: 2.85 (95% CI: 1.19-6.82) in the multivariate analysis. The covariates that were associated with the presence of bone fractures were being over 60 years (OR: 2.74, 95% CI: 1.12-6.69) and having been on hemodialysis for more than 5 years (OR: 6.72, 95% CI: 2.98-15.13). Conclusions: Altered parathyroid hormone is related with bone fractures in hemodialysis patients.

Clinical Impact on Dental Implant Survival in Patients Taking Antiresorptive Medications: A Systematic Review and Meta-Analysis.

Dental implants are a predictable option to replace missing teeth. Patients on antiresorptive medications used to treat disorders associated with bone resorption may need dental implants to replace missing teeth. The data on implant failure in patients on antiresorptive medication requiring dental implants, is conflicting and limited. This systematic review aims to investigate if antiresorptive medications have any clinical impact on dental implant survival. Electronic databases were searched until May 2020. The focus question (PICOS): Participants: humans, Interventions: implant placement surgery in patients on antiresorptive medication, Comparisons: patients on antiresorptive medication vs control (patients not on antiresorptive medication), Outcomes: implant survival, and Study design: clinical studies. The protocol of this systematic review was registered in PROSPERO (CRD42020209083). Fourteen nonrandomized studies were selected for data extraction and risk of bias assessment using the ROBINS-1 tool. Only studies with a control were included for the meta-analysis, 8 articles were included in the meta-analysis using implant-level data, and 5 articles were included in the meta-analysis using patient-level data. There was no statistical significance between the 2 groups at the patient level based on 265 patients. However, there was a statistically significant difference at the implant level based on 2697 implants. Therefore, antiresorptive medications, mainly bisphosphonates (BPs), may significantly contribute to implant failure. Antiresorptive medications, especially BPs may reduce implant survival and impair the osseointegration of dental implants. Failed implants in patients on BPs may not lead to osteonecrosis and may be replaced with success.

Incidencia de Hipocalcemia Post Tiroidectomía. Factores predictores (PTH, Fósforo, Magnesio) y protocolo de manejo con alta precoz / Post-Thyroidectomy Hypocalcemia: Incidence, Prediction, and Outpatient Management Strategies Based on PTH and Calcium Levels

Se ha propuesto la medición de PTH como predictor de hipocalcemia postoperatoria transitoria y permanente. No hay un estándar de punto de corte o tiempo de toma de muestra. El OBJETIVO es reportar la incidencia de hipocalcemia post tiroidectomía en un grupo quirúrgico de alto volumen y proponer un protocolo de manejo ambulatorio (esquemas de I a V) según niveles postoperatorios (PO) de calcemia, PTHi (normal, baja o indetectable) y síntomas. Y determinar valores de PTH postoperatoria como predictores de hipocalcemia. En 106 pacientes con tiroidectomía total entre 2019 y 2021 se realiza medición de niveles pre y postoperatorios de calcio, magnesio, fosforo y PTHi. Se observó 29% y 1% de hipocalcemia transitoria ( 12 meses). Los puntos de corte para predecir hipocalcemia fueron PTH < 8,8 pg/ml y < 80% de descenso de % de PTH (d % PTH) al día siguiente. Con el manejo propuesto se indica el alta precoz (promedio 1.05 días) y el costo de la prescripción es acotado. No hay asociación significativa de hipomagnesemia e hiperfosfemia PO con la hipocalcemia PO. El tratamiento más utilizado es de carbonato de calcio exclusivo (esquemas I y II). Los pacientes se mantienen con síntomas leves a las 2 semanas PO en 5% y logran suspender el tratamiento vía oral en 93% en este mismo período. Los protocolos de medición de PTH como predictor de hipocalcemia son muy variados. Cada centro debe conocer y establecer sus propios protocolos de manejo. Con esta experiencia demostramos la utilidad y seguridad de un esquema de manejo basado en calcemia, PTH (normal, baja o indetectable) y síntomas, con indicación de tratamiento profiláctico para todos los pacientes y ajuste ambulatorio seguro y de menor costo que una hospitalización prolongada.

INTRODUCTION: PTH measurement has been proposed to predict transient and permanent postoperative hypocalcemia. There is no standard cut-off point or time for sampling. Aim: To report the incidence of post-thyroidectomy hypocalcemia in a high-volume surgical group and propose an outpatient management protocol according to postoperative (PO) calcium levels, iPTH (normal, low, or undetectable), and symptoms. Furthermore, determine postoperative PTH values as predictors of hypocalcemia. Methods: In 106 patients with total thyroidectomy between 2019 and 2021, pre-and postoperative levels of calcium, magnesium, phosphorus, and iPTH were measured. Results: Transient ( 12 months) hypocalcemia was observed in 29% and 1%. Cut-off points to predict hypocalcemia were PTH < 8.8 pg/mL and < 80% decrease in % PTH (d% PTH) the day after surgery. With the proposed management, early discharge is indicated (an average of 1.05 days), and the prescription cost is limited. There is no significant association between PO hypomagnesemia and hyperphosphatemia with PO hypocalcemia. The most widely used treatment is exclusive calcium carbonate (schemes I and II). Patients remain with mild symptoms at two weeks PO in 5% and discontinue oral treatment in 93% in this period. Conclusions: Protocols for measuring PTH as a hypocalcemia predictor vary. Each center must know and establish its management protocols. With this experience, we demonstrate the usefulness and safety of a management scheme based on calcium, PTH (normal, low, or undetectable), and symptoms with an indication of prophylactic treatment for all patients and a safe outpatient setting at a lower cost than prolonged hospitalization.

Big data-based parathyroid hormone (PTH) values emphasize need for age correction.

PURPOSE: We aimed to study the relationship between aging and increased parathyroid hormone (PTH) values. METHODS: We performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method. RESULTS: Our sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1-84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer. CONCLUSION: We observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The "old" cross-talk between kidney and bone (classically known as "renal osteodystrophies") has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of "osteoporosis" emerges in nephrology as a new possibility "if results will impact clinical decisions". Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

Polymorphisms in hormonal-related genes might be associated with variations in permanent tooth crown size.

BACKGROUND: The variability in tooth crown size (TCS) is influenced by genetic factors and might be regulated by the difference in hormonal response. MATERIALS AND METHODS: This study aimed to evaluate the association between variations in TCS of permanent teeth with associated factors and genetic polymorphisms in hormonal-related genes (ESR1, ESR2 and PTH). This cross-sectional study involved dental casts from 86 individuals of both sexes. Dental casts were used to determine the maximum TCS of all fully erupted permanent teeth (except third molars) in the mesiodistal (MD) and buccolingual (BL) dimensions. Data such as sex, ethnicity, dental group (incisor, canine, premolar and molar), dental arch (upper and lower) and genetic polymorphisms of hormonal-related genes were used. The DNA from each patient was collected to evaluate the genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and PTH (rs694, rs6256 and rs307247) through real-time PCR. The data were submitted to statistical analysis with a significance level of 0.05. RESULTS: In the MD dimension, the sex, dental group and dental arch were associated with variation in TCS (P < .05). In the BL dimension, the sex, dental group, dental arch and polymorphism in rs694 and rs307247 were associated with variation in TCS. CONCLUSIONS: In short, this study suggests that genetic polymorphisms of PTH are associated with variations in the BL TCS of permanent human teeth.

Enhanced bone tissue regeneration with hydrogel-based scaffolds by embedding parathyroid hormone in mesoporous bioactive glass.

OBJECTIVES: To evaluate hydrogel-based scaffolds embedded with parathyroid hormone (PTH)-loaded mesoporous bioactive glass (MBG) on the enhancement of bone tissue regeneration in vitro. MATERIALS AND METHODS: MBG was produced via sol-gel technique followed by PTH solution imbibition. PTH-loaded MBG was blended into the hydrogels and submitted to a lyophilisation process associated with a chemical crosslinking reaction to the production of the scaffolds. Characterisation of the MBG and PTH-loaded MBG scaffolds, including the scanning electron microscope (SEM) connected with an X-ray detector (EDX), Fourier transform infrared (FTIR), compression strength, rheological measurements, swelling and degradation rates, and PTH release analysis, were performed. Also, bioactivity using simulated-body fluid (SBF), biocompatibility (MTT), and osteogenic differentiation analyses (von Kossa and Alizarin Red stainings, and µ-computed tomography, µCT) of the scaffolds were carried out. RESULTS: SEM images demonstrated MBG particles dispersed into the hydrogel-based scaffold structure, which was homogeneously porous and well interconnected. EDX and FTIR revealed large amounts of carbon, oxygen, sodium, and silica in the scaffold composition. Bioactivity experiments revealed changes on sample surfaces over the analysed period, indicating the formation of carbonated hydroxyapatite; however, the chemical composition remained stable. PTH-loaded hydrogel-based scaffolds were biocompatible for stem cells from human-exfoliated deciduous teeth (SHED). A high quantity of calcium deposits on the extracellular matrix of SHED was found for PTH-loaded hydrogel-based scaffolds. µCT images showed MBG particles dispersed into the scaffolds' structure, and a porous, lamellar, and interconnected hydrogel architecture. CONCLUSIONS: PTH-loaded hydrogel-based scaffolds demonstrated consistent morphology and physicochemical properties for bone tissue regeneration, as well as bioactivity, biocompatibility, and osteoinductivity in vitro. Thus, the scaffolds presented here are recommended for future studies on 3D printing. CLINICAL RELEVANCE: Bone tissue regeneration is still a challenge for several approaches to oral and maxillofacial surgeries, though tissue engineering applying SHED, scaffolds, and osteoinductive mediators might help to overcome this clinical issue.

Epidemiology of Vitamin D (EpiVida)-A Study of Vitamin D Status Among Healthy Adults in Brazil.

Context: There are few studies of 25-hydroxyvitamin D (25(OH)D) concentrations in healthy adults in Brazil. Objective: This work aimed to estimate the prevalence of vitamin D status and its association with lifestyle, sociodemographic, and anthropometric data in 3 regions of Brazil. Methods: A cross-sectional study was conducted among blood donors of both sexes, living in the cities of Salvador, São Paulo, and Curitiba during summer. Blood samples were collected during the procedure. Serum 25(OH)D and parathyroid hormone (PTH) were measured in the same laboratory using chemiluminescence immunoassays. Lifestyle, sociodemographic, and anthropometric data were gathered by an interview with a standardized questionnaire. Vitamin D deficiency and insufficiency was defined as 25(OH)D levels below 20 ng/mL and below 30 ng/mL, respectively. Results: A total of 1004 healthy adults were evaluated with mean levels of 25(OH)D (28.7 ± 9.27 ng/mL) and PTH (34.4 ± 15.1 pg/mL). The standardized prevalence of vitamin D deficiency and insufficiency was in the study population 15.3% and 50.9%: in Salvador 12.1% and 47.6%, in São Paulo 20.5%, and 52.4% and in Curitiba 12.7% and 52.1%, (P = .0004). PTH levels were negatively correlated with 25(OH)D levels. Greater body mass index (BMI) and higher latitude were significant predictors of vitamin D deficiency, whereas skin color (White), longer duration of sun exposure, and current use of dietary supplement were protective. Conclusion: This study confirmed the high prevalence of vitamin D deficiency and insufficiency even in the midsummer in a healthy population of Brazil. Vitamin D levels are associated with sun exposure, latitude, BMI, skin color, and use of supplements.

Pseudohypoparathyroidism: an endocrine orphan disease. case report

Introduction: Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterized by resistance to the parathyroid hormone. There are few reports on PHP in Colombia, so the publication of the present case contributes to increase the interest in its research in the clinical setting. Case presentation: An 18-year-old male with a history of hypothyroidism diagnosed at 4 months of age, stunted growth, delayed puberty, obesity, brachydactyly, pathologic fractures, femoral osteochondroma, insomnia, paresthesia, and chronic constipation was referred to the endocrinology service of a tertiary care center in Bogotá (Colombia) after being hospitalized following a seizure episode. On admission, laboratory tests revealed hypocalcemia, hyperphosphatemia, 25-hydroxy vitamin D in the range of insufficiency and elevated PTH. Imaging studies showed heterotopic ossifications and calcifications of the basal ganglia. A genetic study confirmed the diagnosis of PHP1A, so treatment was started with calcium, cholecalciferol and phosphorus chelators, leading to a satisfactory course. Both the patient and his first-degree relatives received genetic counseling and interdisciplinary assessment. Conclusion: Although PHP type 1A is an unrecognized complex genetic disorder, it has a critical clinical importance within the differential diagnoses of hypocalcemia. Without prompt diagnosis and treatment, patients may experience serious and potentially fatal metabolic consequences.

Introducción. El seudohipoparatiroidismo (SPT) es un trastorno genético poco frecuente que se caracteriza por la resistencia a la hormona paratiroidea (PTH). En Colombia existen pocos reportes sobre esta enfermedad, por lo que la publicación del presente caso contribuye a aumentar el interés en su búsqueda en el ámbito clínico. Presentación del caso. Hombre de 18 años con antecedente de hipotiroidismo (diagnosticado a los 4 meses de nacido), retraso del crecimiento, desarrollo puberal tardío, obesidad, braquidactilia, fracturas patológicas, osteocondroma femoral, insomnio, parestesias y estreñimiento crónico, quien asistió al servicio de endocrinología de un hospital de tercer nivel de Bogotá (Colombia) remitido luego de haber estado hospitalizado por un episodio convulsivo. En dicha hospitalización los laboratorios evidenciaron hipocalcemia, hiperfosfatemia y 25-OH vitamina D en rango de insuficiencia con niveles elevados de PTH, y los estudios imagenológicos demostraron osificaciones heterotópicas y calcificaciones de ganglios basales del cerebro. Al paciente se le realizó un estudio genético que confirmó el diagnóstico de SPT1A, por lo que se le inició manejo con suplencia de calcio, colecalciferol y quelantes de fósforo, con lo cual evolucionó satisfactoriamente. Tanto el paciente como sus familiares de primer grado recibieron asesoramiento y valoración interdisciplinaria. Conclusiones. El SPT1A es un trastorno genético complejo poco conocido pero de alta importancia clínica dentro de los diagnósticos diferenciales de hipocalcemia que debe considerarse ya que sin el diagnóstico y tratamiento oportunos, los pacientes pueden presentar consecuencias metabólicas graves y potencialmente fatales.

Valor pronóstico de la parathormona postoperatoria de 24 horas en el manejo de la hipocalcemia tras tiroidectomía total en un hospital de Valencia durante 2012-2019 / Prognostic value of 24-hour postoperative parathormone in the management of hypocalcemia after total thyroidectomy in a hospital in Valencia during 2012-2019

Introducción: La hipocalcemia por hipoparatiroidismo es la complicación más frecuente tras tiroidectomía total. Un factor predictor importante de hipocalcemia es la parathormona postoperatoria, pero el momento en el que otorga mejores resultados predictivos aún se discute. Objetivo: El objetivo es analizar el valor pronóstico de la parathormona postoperatoria a las 24 horas como indicador de hipocalcemia, en comparación con la seriación de los niveles de calcio. Metodología: Estudio observacional retrospectivo y descriptivo de 297 pacientes intervenidos de tiroidectomía total durante ocho años. Los pacientes fueron clasificados en tres grupos de riesgo según la parathormona postoperatoria (alto, medio y bajo riesgo). Para comparar la parathormona frente al calcio postoperatorio como predictor de hipocalcemia, se obtuvieron curvas ROC y áreas debajo de la curva. Resultados: El riesgo relativo de tener hipocalcemia con parathormona ≤15 pg/mL es de 353,4 (p = 0,00). La prueba de parathormona postoperatoria (≤15 pg/mL a las 24 h) obtuvo una sensibilidad del 96,25 % para la detección de hipocalcemia, especificidad del 94,06 % y precisión global del 95,03 %. El grupo de alto riesgo (parathormona ≤15 pg/mL) concentra la mayoría de los pacientes con hipocalcemia, y abarca la totalidad de los casos permanentes. Conclusiones: La parathormona postoperatoria a las 24 horas de la tiroidectomía total es un test con un valor pronóstico considerable, capaz de predecir el riesgo de hipocalcemia postquirúrgica. Se encontró que los pacientes con parathormona >15 pg/mL pueden ser dados de alta de manera segura.

Introduction: Hypocalcemia due to hypoparathyroidism is the most frequent complication after total thyroidectomy. An important predictive factor of hypocalcaemia is postoperative parathormone (PTH), but the optimal time for testing PTH levels is under discussion. Objectives: The objective is to analyze the prognostic value of postoperative PTH at 24 hours as an indicator of hypocalcaemia, compared to serum calcium levels. Methodology: Descriptive retrospective observational study of 297 patients who underwent total thyroidectomy over an 8-year period. The patients were classified into 3 risk groups according to postoperative parathormone (high, medium and low risk). To compare parathormone versus postoperative calcium as a predictor of hypocalcemia, ROC curves and areas under the curve (AUC) were obtained. Results: The relative risk of having hypocalcemia with parathormone ≤ 15 pg/mL is 353.4 (p = 0.00). The postoperative parathormone test (≤ 15 pg / mL at 24h) obtained a sensitivity of 96.25% for the detection of hypocalcemia, specificity of 94.06% and global precision of 95.03%. The high-risk group (parathormone ≤ 15 pg/mL) accounts for the vast majority of patients with hypocalcemia and covers all permanent cases. Conclusions: Postoperative levels 24 hours after total thyroidectomy is a test with considerable prognostic value, capable of predicting the risk of postsurgical hypocalcemia. Patients with levels over > 15 pg/mL can be safely discharged.